Social Withdrawal Following Trauma Exposure: a Neuroeconomic Approach

项目摘要/摘要 社会功能受损是创伤相关疾病的常见和致残后果。虽然 社交退缩会在创伤暴露人群中导致广泛的残疾，但人们对这种情况知之甚少。 这种功能障碍背后的神经生物学机制。在这个项目中，创伤后的社交退缩 暴露被概念化为大脑奖赏通路中的失调所致。申请人 建议使用神经经济学范式，信任任务，来探索社会奖励功能的变化 受创伤影响的人群。应激肽--脑下垂体腺苷环化酶激活的可能作用 多肽(PACAP)，与压力暴露后社会行为的变化有关，将被确定。这个 中心假设是，在创伤暴露人群中，社会退缩的程度(社会退缩) 网络规模)将通过信任任务行为和异常奖励相关神经的变化来预测 腹侧纹状体、背侧纹状体和内侧前额叶皮质中的信号。指导以病人为本 研究职业发展奖将研究和培训活动结合起来，以支持申请者的 长期目标是开发一个独立的研究计划，将神经经济学范式应用于 焦虑和情绪障碍的维度模型。第一个培训目标是发展申请者的专业知识 研究创伤和创伤后应激障碍。这将通过由伊莎贝尔提供的密集指导来支持 罗索博士，创伤后应激障碍神经化学专家，克里·雷斯勒，医学博士，博士，创伤后应激障碍 麦克莱恩医院/哈佛医学院(HMS)的创伤后应激障碍翻译神经科学。第二 培训的目的是发展功能磁共振成像范例设计和神经经济学数据分析方面的专业知识。这将是 由情感神经科学专家Diego Pizzagalli博士提供指导，并通过 咨询McLean医院/HMS的功能磁共振专家Blaise Frederick博士，以及 通过咨询弗吉尼亚理工大学Carilion Research的神经经济学专家里德·蒙塔古博士 研究所。第三个培训目标是发展应激神经内分泌学方面的专业知识，包括应激肽。 以及它们与卵巢激素的相互作用。这一目标将得到雷斯勒博士的支持，他最初 确定了PACAP与人类创伤后应激障碍的关系。训练的计划已经被仔细地安排好了 计划在授权期结束前将申请者定位为研究独立性。的贡献 拟议的研究将通过识别行为、神经和分子生物标记物来推动该领域的发展 创伤暴露女性中的社交快感缺乏和社交退缩。通过使用神经经济学范式来 这项拟议的研究描述了导致社交退缩的奖励回路的变化 代表着与现状的实质性背离。总而言之，拟议的项目将提供 应聘者在创伤后应激障碍研究和功能神经成像方面有扎实的基础，同时也有进步 了解创伤暴露后社交退缩的神经机制。

Project Summary/Abstract Impaired social functioning is a frequent and disabling consequence of trauma-related disorders. Although social withdrawal results in widespread disability in trauma-exposed populations, little is known about the neurobiological mechanisms underlying this dysfunction. In this project, social withdrawal following trauma exposure is conceptualized as resulting from dysregulation within brain reward pathways. The applicant proposes to use a neuroeconomic paradigm, the Trust Task, to probe alterations in social reward functioning in trauma-exposed populations. Possible contributions of a stress peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), implicated in changes in social behavior following stress exposure, will be identified. The central hypothesis is that in trauma-exposed populations, the extent of social withdrawal (decreased social network size) will be predicted by alterations in both Trust Task behavior and abnormal reward-related neural signaling in the ventral striatum, dorsal striatum, and medial prefrontal cortex. This Mentored Patient-Oriented Research Career Development Award combines research and training activities to support the applicant's long-range goal of developing an independent research program applying neuroeconomic paradigms within dimensional models of anxiety and mood disorders. The first training aim is to develop the applicant's expertise in research on trauma and PTSD. This will be supported through intensive mentorship, provided by Isabelle Rosso, Ph.D., an expert on PTSD neurochemistry, and Kerry Ressler, M.D., Ph.D., an expert in the translational neuroscience of PTSD, both of McLean Hospital/ Harvard Medical School (HMS). The second training aim is to develop expertise in fMRI paradigm design and analysis of neuroeconomic data. This will be supported via mentorship by Diego Pizzagalli, Ph.D., an expert in affective neuroscience, and through consultation with Blaise Frederick, Ph.D., an expert on fMRI, both at McLean Hospital/ HMS, as well as through consultation with Read Montague, Ph.D., a neuroeconomics expert at Virginia Tech Carilion Research Institute. The third training aim is to develop expertise in stress neuroendocrinology, including stress peptides and their interactions with ovarian hormones. This aim will be supported by Dr. Ressler, who originally identified the relationship between PACAP and PTSD in humans. The program of training has been carefully planned to position the applicant for research independency by the end of the award period. The contribution of the proposed research will advance the field by identifying behavioral, neural, and molecular biomarkers for social anhedonia and social withdrawal in trauma-exposed women. By using neuroeconomic paradigms to characterize alterations in reward circuitry that contribute to social withdrawal, the proposed research represents a substantive departure from the status quo. To summarize, the proposed project will provide the applicant with a strong foundation in PTSD research and functional neuroimaging, while also advancing understanding of the neural mechanisms underlying social withdrawal following trauma exposure.